Recapping Q1 2024 FDA Decisions in Cardiology, with Deepak Bhatt, MD, MPH, MBA

Few, if any fields, can lay claim to witnessing the consistent level of advancement that exists within cardiovascular medicine.

Even with such a historic rate of breakthroughs, advancements, and public health-altering discoveries the field has experienced in the last century, the pace of furtherance the field has experienced in recent years sets it apart from most, if not all other specialties in medicine. An example of the fruits bared by these past several years of innovation was the sheer onslaught of regulatory approvals and expansions for the field from the US Food and Drug Administration in the first 90 days of 2024.

In March 2024 alone, the community has seen a historic label expansion for semaglutide as the first obesity-specific agent with an indication for reducing cardiovascular risk, the first new mechanism of action approved for an oral antihypertensive agent in more than 30 years, and a massive label expansion for bempedoic acid to include use for primary and secondary cardiovascular prevention.

Below is a list highlighting our coverage of the various cardio-centric FDA decisions and announcements from Q1 2024:

• February 02: FDA Approves EVOQUE Tricuspid Valve Replacement System for Tricuspid Regurgitation
• February 05: FDA Accepts NDA Submission for Acoramidis in ATTR-CM
• February 14: FDA Panel Votes in Favor of Abbott TriClip for Tricuspid Regurgitation
• March 1: FDA Approves AGENT DCB for In-Stent Restenosis
• March 8: Semaglutide (Wegovy) Receives FDA Label Expansion to Include Cardiovascular Risk Reduction
• March 11: Alirocumab Approved for Heterozygous Familial Hypercholesterolemia in Patients 8 Years and Older
• March 20: FDA Approves Aprocitentan (Tryvio) for Treatment-Resistant Hypertension
• March 22 Bempedoic Acid Wins FDA Approval for Reducing Cardiovascular Risk in Primary, Secondary Prevention
• March 22: FDA Approves Single-Tablet Macitentan, Tadalafil Combination (Opsynvi) for Pulmonary Arterial Hypertension

With an interest in learning more about the community’s reaction to these approvals and how they influence care, we sat down with opinion leader Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Heart and the Dr. Valentin Foster Professor of Cardiovascular Medicine, for his perspective.

Deepak Bhatt, MD, MPH, MBA, on CV Advances in Q1 2024

HCPLive: How exciting has it been for you to witness such an onslaught of significant approvals and clearances across various domains of cardiovascular illness in the first quarter of 2024?

Deepak Bhatt, MD, MPH, MBA: What a great question. I think times are booming for cardiology and cardiovascular medicine in general, just as you allude to so many approvals of novel drugs and devices. So, people that are saying, "Oh, what's going on in cardiology? Has it peaked? Is there still going to be innovation?" Well, yeah, there's just been a lot of innovation even very recently. I think it'll keep going and there is no sign of it abating. So, to me, this is really exciting.

It's also good to see that the regulatory agencies, the FDA is the one you're alluding to here, are so receptive to novel therapies. That then provides positive feedback to folks out there in industry that are developing novel drugs and devices and, ultimately, the patients who can benefit from these that, in the right patients, every one of the innovations you mentioned, can be really life-changing and, in some cases, lifesaving. So, I'm super excited by the current climate in cardiology, in terms of drug and device discovery, including regulatory approvals.

HCPLive: As new data surrounding benefits in areas outside of diabetes emerges, how impact is the recent announcement of CMS coverage for an agent like semaglutide in management of cardiovascular disease on a population health level?

Deepak Bhatt, MD, MPH, MBA: I think that's a terrific question and I think it's huge. When there's a well done randomized, placebo-controlled trial, that can be practice changing and it looks like that is what is happening here, appropriately.

So, first, it starts with regulatory approvals, and then coverage decisions, because obviously, if drugs that are expensive and aren't covered, then it's hard to actually utilize them. So, I think this is a great series of events, terrific data, really strong data consistent with prior datasets, maybe not large, randomized trials, but a lot of good data for semaglutide, even before. Then we've got, at this point in time, strong sorts of regulatory wording around the approvals and, as you're alluding to CMS coverage, but I think other insurance will follow with coverage.

Now, the real goal is implementation science: finding the right patients who can benefit from this sort of drug. I think, unlike a lot of other quote-unquote "cardiovascular drugs", where patients may not be that excited about taking them or taking them long term—lifelong statins are a prime example of that—here, we've got a drug that isn't just reducing cardiovascular outcomes, but in fact, is causing weight loss.

So, I think for a lot of patients, that will be a plus they'll say, "Yeah, I actually want to be on that medicine", as opposed to a situation with say, statins, ACE inhibitors, or something where they may not really feel great about the drug, in some cases, they may even perceive having side effects, whether real or imagined. But here many patients will sort of be our partners and say, "Yeah, I actually want to be on that and I can see the weight loss, so I'm going to stay on it".

The only word of caution I'd say is with the GLP-1 receptor agonists, what's been seen, and this appears to be true for a variety of agents in development as well where they're causing substantial amount of weight loss, that's terrific, but when they stopped the drug the weight does come back and that's not unexpected— when you stop a statin, the LDL-C comes back.The additional risk here is that its largely fat that's coming off, but then when it's going back on—when you stop the drug—it is the fat that comes on board. You can end up sort of with net muscle loss where you know, you are putting on fat, but not putting on muscle. So, you could actually end up worse off, if you go on to drug, lose a bunch of weight, lose fat, and then stop the drug and the fat all comes back, but any muscle mass loss is sort of gone forever.

So, that is important as patients go on these drugs. Sort of like when we tell patients on statins, just because you're on a statin doesn't mean you can eat 2 pieces of cake and ice cream, you've got to still watch your diet. It is the same sort of thing here, just because you go on a GLP-1 receptor agonist, say semaglutide in this case, it does not mean that you can then forget about exercise, good diet, and that sort of thing—you still want to do that.

In particular, it's important here as you're losing weight to maintain muscle mass and if for some reason the drug is discontinued due to side effects, hopefully not but the potential cost issues, or something, that person does not then end up just regaining all that weight, but now all its fat with really net loss of muscle so they're actually worse off than they were predrug.

Just an important caveat. It does not mean that our job in terms of being preventionists ends just because there is a drug and a series of drugs coming out, that will be so effective at weight loss and have cardiovascular benefits.

HCPLive: How impactful is the recent label change for bempedoic acid in terms of risk management for primary and secondary patient populations?

Deepak Bhatt, MD, MPH, MBA: I think these sorts of label changes do matter a lot. I mean, not every physician is necessarily reading the label probably shouldn't, but not everyone does. But I think nonetheless, it does translate into practice, it does translate into coverage by third party payers, and so forth. So, I think that the bempedoic acid is a really useful addition to the prevention armamentarium. Certainly, from what we saw from CLEAR Outcomes, it seems to be quite safe overall, but, in particular, for patients that just can't or won't take statins. It's a great oral therapy, especially combined with ezetimibe. With that combination, you can get pretty potent LDL lowering and folks should not really have side effects from ezetimibe, it's not systemically really absorbed or causing side effects in the vast majority of people. So, as a combination you can get pretty good LDL lowering.

I think that the addition of bempedoic acid to the number of options to control LDL is great and I'm happy that the labeling reflects that. More real-world experience will accumulate with bempedoic acid as physicians become more comfortable with using it. So, I was happy to see that as well.